Genome-Wide Association of Heroin Dependence in Han Chinese

PLoS One. 2016 Dec 9;11(12):e0167388. doi: 10.1371/journal.pone.0167388. eCollection 2016.

Abstract

Drug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10-7) and BRSK2 (BR serine/threonine 2; p = 4.110-6). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field.

MeSH terms

  • Adult
  • Asian People / genetics
  • China / epidemiology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Heroin Dependence / epidemiology
  • Heroin Dependence / genetics*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Genetic*
  • Protein Serine-Threonine Kinases / genetics
  • Rho Guanine Nucleotide Exchange Factors / genetics

Substances

  • ARHGEF10 protein, human
  • Rho Guanine Nucleotide Exchange Factors
  • Brsk2 protein, human
  • Protein Serine-Threonine Kinases